Autism Spectrum Disorder Development Research Articles

Neurodevelopmental disorders in children with cleft lip and palate: a systematic review.

Individuals with orofacial clefts (OFCs) may be at an increased risk of developing autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD). This systematic review provides a summary of the most recent data regarding the prevalence of ASD and ADHD in the OFC population and compares this to the general paediatric population. Multiple databases were searched including PubMed/Medline and Embase in July 2024, following the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines and was registered in PROSPERO (CRD42024565219). 1025 papers were identified for screening, of which nine were included in the report. Percentage prevalence was calculated and compared to global prevalence or control populations where available. Overall, ASD prevalence among children with a cleft ranged from 0 to 50% (Mean = 2.87%; SD = 5.40) compared to ~ 1% globally (WHO) and ADHD prevalence ranged from 2.34 to 31.71% (Mean = 3.63%; SD = 4.30) compared to ~ 5% globally (NICE). Matched control populations showed larger differences. Isolated cleft palate was associated with higher rates than isolated cleft lip or combined cleft lip and palate. Prevalence in individuals with syndromic clefts appeared greater still (Mean = 14.80%; SD = 16.58) although populations were small. Children with OFCs demonstrate increased prevalence of ASD compared to the average paediatric population. Evidence for increased prevalence of ADHD is less clear, with varying rates across studies. Children with isolated cleft palate or cleft associated with genetic syndromes appear most at risk, although further research is needed.

The Correlation Between Screen Time and the Probability of Developing Autism Spectrum Disorder.

Background Autism spectrum disorders (ASDs) are a collection of neurological, psychological, and developmental anomalies that manifest in early life, affecting individuals across all racial, cultural, and socioeconomic groups. Its prevalence has grown significantly over the past 20 years. Exposure to digital devices has increased alongside the rise in ASD prevalence. Research suggests that prolonged screen time can negatively impact a child's brain development, language, literacy, and cognitive function. The aim of this study was to investigate the correlation between screen time and the probability of developing autism spectrum disorder. Methodology This study employed a case-control design to examine 231 children in Zakho City diagnosed with an autism spectrum disorder. The study was conducted from October 1, 2023, to March 1, 2024. The participants included neurotypical individuals and individuals with autism. Data were gathered through standardized questionnaires and analyzed using IBM SPSS Statistics for Windows, Version 26(Released 2019; IBM Corp., Armonk, New York). The study was approved by the College of Medicine/University of Zakho, Kurdistan Region, Iraq, and ethical permission was obtained. Results The study revealed a uniform age distribution between cases and controls, with a majority of male participants and a smaller percentage of female participants. ASD patients had a significantly longer duration of exposure to electronic devices compared to controls, with cases averaging 3.61 hours of screen time daily (t-test: t = 0.0001). Conclusion In summary, screens have a major impact on children's neurodevelopment and may increase their risk of developing ASD. However, no appreciable distinction was observed between children diagnosed with ASD and those without regarding early exposure to screens. Our findings can be used to create guidelines for children's media consumption and to raise awareness of this issue. Further research is needed to evaluate the association.

Prenatal Diabetes and Obesity: Implications for Autism Spectrum Disorders in Offspring - A Comprehensive Review.

Fetal brain development is an important determinant of neuropsychological performance in children. Any alterations in the intrauterine environment at different stages of pregnancy, such as maternal metabolic disorders, can lead to the development of chronic conditions in the offspring. Therefore, maternal diabetes, especially gestational diabetes mellitus, is an important factor in the development of pathological changes, such as miscarriage, fetal macrosomia, or neurodevelopmental disorders. During pregnancy, the hyperglycemic intrauterine environment adversely affects fetal brain development. A growing body of scientific research indicates that prenatal environmental factors, by affecting fetal brain development, can contribute to the appearance of autism spectrum disorders. According to the latest estimates from the International Diabetes Federation (2021), approximately 21.1 million live births worldwide (16.7%) have been affected by some form of hyperglycemia during pregnancy. The condition is more prevalent in low- and middle-income countries, where access to obstetric care is limited. The following factors have been identified as potential risk factors for gestational diabetes: advanced maternal age, overweight and obesity, family history of diabetes, and any form of diabetes. The purpose of this review is to summarize recent studies evaluating the effect of prenatal and maternal risk factors such as maternal pre-pregnancy diabetes, gestational diabetes, and obesity on the risk of developing autism spectrum disorder in offspring.

Association of MTHFR C677T, MTHFR A1298C polymorphism in relation to patients with autism in Thi-Qar Governorate

Background. Recent data suggests that environmental factors may account for up to 40-50% of the variability in the risk of developing autism spectrum disorder (ASD). Aim. The purpose of this study was to examine the correlation between MTHFR polymorphism and the heightened susceptibility to autism in children with autism in Thi-Qar. Material and method. A comparison case-control study of blood samples collected from a cohort of 100 individuals diagnosed with autism, along with 100 healthy individuals serving as a control group. The participants were divided into two groups. The first group, known as the control group, consisted of one hundred healthy people aged between 3 and 14 years. The second group consisted of one hundred autistic patients, ranging in age from 3 to 14 years old. Results. The findings demonstrated a noteworthy elevation in the gene expression of MTHFR C677T and MTHFR A1298C in all groups of patients, in comparison to the control group. The current study showed a significant difference at p-value <0.05 was recorded the highest genotype was CT in autism patients 85% and in control group 1.43%, while the lowest genotype was TT 5% in autism patients, and in the control group 1.43%. Within the haplotype, a non-significant difference was noted at p-value <0.05, showing that the highest allele was C in the control group at 97.18%, and in autism patients at 51.35%. According to the odds ratio, it showed a significant gene frequency in autism patients than in the control group. The current study showed that a significant difference at p-value <0.05 was recorded in the highest AC genotype in autism patients at 85%, and in the control group 2.86%, while the lowest genotype was CC 4% in autism patients, and in the control group 0%. Within the genotype, a significant different at p-value <0.05 was noted, showing that the highest allele was A in the control group at 97.22%, and T in autism patients at 51.89%. Conclusion. The study data indicates a higher likelihood of ASD in individuals with the MTHFR C677T CT/CC and MTHFR A1298C AC/CC polymorphisms, suggesting a potential involvement of abnormalities in the folate/methylation cycle in autism.

Gestational age and sex interaction and risk for autism spectrum disorder in extremely preterm newborns: an 18‑month follow‑up study

IntroductionExtremely preterm newborns - EPTN (born ≤28 weeks gestational age) are at increased risk of developing autism spectrum disorders (ASD). Demographic and perinatal risk factors associated with ASD risk in EPTN are understudied.Objectives(i) In EPTN and born at full-term healthy controls (HC), to characterize the emergence of ASD traits and autistic symptom load at age 18 months; (ii) in EPTN, to identify the influence of perinatal characteristics such as sex and gestational age on autistic symptom load at corrected-age 18 months.MethodsObservational, longitudinal, prospective, 18-month follow-up study. We recruited a cohort of n=113 EPTN and n=47 HC (the PremTEA cohort); n=57 EPTN and n=42 HC successfully completed the 18-month follow-up visit. We assessed autistic symptom load & risk at 18 months using the M-CHAT-R/F questionnaire. For all EPTN and HC, we collected demographic and perinatal data. Using GLMs, we assessed, in EPTN, the association between demographic/perinatal variables and 18-month autistic symptom levels.ResultsAt 18 months, EPTN children showed higher autistic symptom levels than HC (M-CHAT-R/F score, mean (SD) [range] = 2.21 (3.23) [0-12] in EPTN vs. 0.33 (0.57) [0-2] in HC; d=.873, p=.001. In EPTN, we identified differences by gestational age and sex in autistic symptom levels at 18 months (aR2=0.517, p=.006). In particular, female EPTNs born with lower gestational age showed higher autistic symptom load at age 18 months.ConclusionsOur findings support the need for early screening of ASD symptomatology in EPTN infants, particularly in higher-risk subgroups, such as female patients born with lower gestational ages.Disclosure of InterestNone Declared

Associations between genetically determined dietary factors and risk of autism spectrum disorder: a Mendelian randomization study.

Existing studies confirm the importance of dietary factors in developing autism spectrum disorder (ASD) and disease progression. Still, these studies are primarily observational, and their causal relationship is unknown. Moreover, due to the extensive diversity of food types, the existing research remains somewhat limited in comprehensiveness. The inconsistency of the results of some studies is very disruptive to the clinic. This study infers a causal relationship between dietary factors on the risk of developing ASD from a genetic perspective, which may lead to significant low-cost benefits for children with ASD once the specificity of dietary factors interfering with ASD is confirmed. We performed a two-sample Mendelian randomization (MR) analysis by selecting single nucleotide polymorphisms (SNPs) for 18 common dietary factors from the genome-wide association study (GWAS) database as instrumental variables (IVs) and obtaining pooled data for ASD (Sample size = 46,351) from the iPSYCH-PGC institution. Inverse variance weighted (IVW) was used as the primary analytical method to estimate causality, Cochran's Q test to assess heterogeneity, the Egger-intercept test to test for pleiotropy and sensitivity analysis to verify the reliability of causal association results. The MR analysis identified four dietary factors with potential causal relationships: poultry intake (fixed-effects IVW: OR = 0.245, 95% CI: 0.084-0.718, P < 0.05), beef intake (fixed-effects IVW: OR = 0.380, 95% CI: 0.165-0.874, P < 0.05), cheese intake (random-effects IVW: OR = 1.526, 95% CI: 1.003-2.321, P < 0.05), and dried fruit intake (fixed-effects IVW: OR = 2.167, 95% CI: 1.342-3.501, P < 0.05). There was no causal relationship between the remaining 14 dietary factors and ASD (P > 0.05). This study revealed potential causal relationships between poultry intake, beef intake, cheese intake, dried fruit intake, and ASD. Poultry and beef intake were associated with a reduced risk of ASD, while cheese and dried fruit intake were associated with an increased risk. Other dietary factors included in this study were not associated with ASD.

Longitudinal analysis of sensory responsivity from infancy to school age in children at high and low familial likelihood for autism

AbstractBackgroundEmpirical evidence regarding the development of sensory responsivity in young children at high likelihood to develop autism spectrum disorder (ASD) remains relatively limited. It is unclear how sensory responsivity behaviors may change over time and impact later developmental outcomes. The goals of this study were to (a) characterize developmental trajectories of sensory responsivity across infancy (∼12 months), toddlerhood (∼24 months), and school age (6–11 years) in children at high and low familial likelihood for ASD; and (b) determine if sensory responsivity in infancy predicts adaptive and cognitive functioning at school age among children with ASD.MethodsGeneralized linear mixed effects models were used to examine scores from the Sensory Experiences Questionnaire in three groups of children including high‐likelihood children later diagnosed with ASD (HL‐ASD; n = 30), high‐likelihood children without ASD (HL‐Neg; n = 150), and low‐likelihood control children not meeting ASD diagnostic criteria (LL‐Neg; n = 94). Hierarchical linear regression was then used to examine the association between sensory responsivity scores in infancy and functional adaptive and cognitive outcomes at school age for children at high likelihood of ASD.ResultsDevelopment of sensory responsivity from infancy to later childhood is best estimated by the effects of chronological age and Group for Sensory Seeking and Hypo responsivity and the additional effect of the interaction of Group and chronological age for Total and Hyper responsivity. Early elevated Hypo responsivity and Sensory Seeking scores are negatively associated with later adaptive behavior but not cognitive level.ConclusionOverall, higher degrees of Sensory Seeking and Hypo sensory responsivity are detectable in autistic children's behavioral repertoires by 12 months of age and associate with reduced adaptive functioning in middle childhood. These results point to the potential importance of early detection and treatment implications of early sensory behaviors.

Прогнозування ризику розвитку розладів аутистичного спектра в дітей з епілептичними енцефалопатіями

Predicting the risk of developing autism spectrum disorders (ASD) in children with epileptic encephalopathies (EE) is an important task, which makes it possible to identify the most significant risk factors and develop ways of their modification. Purpose - to develop a model for predicting the risk of developing ASD in young children with EE. Materials and methods. 75 children aged 0-3 years with the onset of epileptic seizures in the first year of life, clinical manifestations of EE were examined. The most informative clinical, neurophysiological, and neuroimaging indicators for predicting the risk of clinical manifestations of ASD were determined: age of onset of epileptic seizures, index of spike-wave activity during NREM sleep, frequency and amplitude of alpha rhythm, frequency and amplitude of epileptiform activity, fractional anisotropy and mean diffusion coefficient in the Broca’s center, fractional anisotropy in the Wernicke center and knee of the corpus callosum. The multiple linear regression method was used to predict the risk of developing ASD symptoms. Results. A model for predicting the risk of developing clinical manifestations of ASD in children with EE has been developed. It was established that the risk of developing clinical manifestations of ASD increases with a decrease in the age of onset of epileptic seizures, decrease in the frequency and amplitude of the alpha rhythm according to electroencephalography (EEG) data, increase of the index of spike-wave activity, frequency and amplitude of epileptiform activity, increase in the index of fractional anisotropy in the anterior part of the arcuate tract, decrease in the average diffusion coefficient in the area of the Broca’s center, fractional anisotropy in the Wernicke center and the knee of the corpus callosum according to magnetic resonance tractography. Conclusions. A regression model for predicting the risk of clinical manifestations of ASD in children with EE was developed with an average error of approximation of 13.2% and a coefficient of determination of 0.74, which is recommended for use in clinical practice in order to form groups of children at high risk of ASD. Such children require further dynamic monitoring and early intervention by specialists of a multidisciplinary team for timely identification and correction of ASD symptoms The research was carried out in accordance with the principles of the Helsinki Declaration. The study protocol was approved by the Local Ethics Committee of the participating institution. The informed consent of the patient was obtained for conducting the studies. No conflict of interests was declared by the author.

The Selective Social Attention task in children with autism spectrum disorder: Results from the Autism Biomarkers Consortium for Clinical Trials (ABC-CT) feasibility study.

The Selective Social Attention (SSA) task is a brief eye-tracking task involving experimental conditions varying along socio-communicative axes. Traditionally the SSA has been used to probe socially-specific attentional patterns in infants and toddlers who develop autism spectrum disorder (ASD). This current work extends these findings to preschool and school-age children. Children 4- to 12-years-old with ASD (N = 23) and a typically-developing comparison group (TD; N = 25) completed the SSA task as well as standardized clinical assessments. Linear mixed models examined group and condition effects on two outcome variables: percent of time spent looking at the scene relative to scene presentation time (%Valid), and percent of time looking at the face relative to time spent looking at the scene (%Face). Age and IQ were included as covariates. Outcome variables' relationships to clinical data were assessed via correlation analysis. The ASD group, compared to the TD group, looked less at the scene and focused less on the actress' face during the most socially-engaging experimental conditions. Additionally, within the ASD group, %Face negatively correlated with SRS total T-scores with a particularly strong negative correlation with the Autistic Mannerism subscale T-score. These results highlight the extensibility of the SSA to older children with ASD, including replication of between-group differences previously seen in infants and toddlers, as well as its ability to capture meaningful clinical variation within the autism spectrum across a wide developmental span inclusive of preschool and school-aged children. The properties suggest that the SSA may have broad potential as a biomarker for ASD.

Early Screen-Time Exposure and Its Association With Risk of Developing Autism Spectrum Disorder: A Systematic Review.

Autism spectrum disorder (ASD) is a neurological deficit in brain functions that prevents a child from having a normal social life like his peers. It results in the inability to interact and communicate with others. Unsurprisingly, the alarming increase in screen-time exposure in children has become even more of a concern. Electronic devices are a double-edged sword. Despite their benefits, they have many potential hazards to children's neurological development. Previous studies have investigated the effects of unsupervised screen time and its impact on white matter development during the early years of life of children. The white matter has an important role in the development of neurological functions. This systematic review aims to qualitatively analyze the literature available on early screen time exposure and its association with the risk of developing ASD. This systematic review implemented the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) 2020 guidelines. PubMed, PubMed Central (PMC), Google Scholar, and Cochrane Library databases were searched for data in the recent six years. A total of 27,200 articles were identified using the MeSH and keywords through four selected databases. Search results revealed 70 from PubMed, 17,700 from Google Scholar, zero from Cochrane Library, and 9,430 from PubMed Central. After applying filters and screening the results by title and abstract and then by full text, 11 studies fulfilled the criteria to be included in the review. We found that the longer the period of screen exposure, the higher the risk that the child may develop ASD. Further, the earlier the child is exposed to screens, the higher the risk of developing ASD in children compared to children exposed later.

Autism Spectrum Disorder is Related to Increasing Intestinal Prevotella That Can Be Regulated by Vitamin A

Background: Increasing studies suggest that the microbiome-gut-brain axis plays a fundamental role in developing autism spectrum disorder (ASD). Objectives: We aimed to explore biomarkers from gut bacteria in ASD and the dietary vitamin A (VitA) relationship with intestinal bacteria of autistic children and provide a theoretical basis for dietary regulation of ASD. Methods: Ten autistic children aged 2 to 6 from special training facilities were enrolled from 2017 to 2018. At the same time, 10 healthy children aged 2 to 6 from a kindergarten were collected as a control. All participants were from Chongqing, China. The 16sRNA amplicon sequencing was used to analyze children's intestinal bacteria. The serum retinol level was detected by high-performance liquid chromatography (HPLC), and children's dietary intake was analyzed using three-day 24-hour dietary recalls. Results: There were significant differences in alpha diversity between the groups. Also, a higher relative abundance of Prevotellaceae, Prevotella 9, and Roseburia was observed among ASD children. We also found decreases in 9 bacteria (Enterobacteriales, Gammaproteobacteria, Enterobacteriaceae, Clostridiaceae 1, Clostridium sensu stricto 1, Escherichia-Shigella, Bacteroides fragilis, Escherichia coli, and Clostridium neonatale). Dietary VitA intake and serum retinol concentration were lower in the ASD group than in the control group. Meanwhile, serum VitA had a significantly negative correlation with the abundance of intestinal Prevotella 9. Conclusions: Our study helps identify some bacterial biomarkers for ASD, as in previous reports. Meanwhile, the study suggests that dietary VitA may be involved in the clinical symptoms of ASD by regulating the intestinal bacteria Prevotella. It may provide a new way to treat ASD in the future. Further studies are needed to identify the results by expanding the sample size and developing animal experiments.

Early-life differences in the gut microbiota composition and functionality of infants at elevated likelihood of developing autism spectrum disorder

Evidence from cross-sectional human studies, and preliminary microbial-based intervention studies, have implicated the microbiota-gut-brain axis in the neurobiology of autism spectrum disorder (ASD). Using a prospective longitudinal study design, we investigated the developmental profile of the fecal microbiota and metabolome in infants with (n = 16) and without (n = 19) a family history of ASD across the first 36 months of life. In addition, the general developmental levels of infants were evaluated using the Mullen Scales of Early Learning (MSEL) test at 5 and 36 months of age, and with ADOS-2 at 36 months of age. At 5 months of age, infants at elevated-likelihood of ASD (EL) harbored less Bifidobacterium and more Clostridium and Klebsiella species compared to the low-likelihood infants (LL). Untargeted metabolic profiling highlighted that LL infants excreted a greater amount of fecal γ-aminobutyric acid (GABA) at 5 months, which progressively declined with age. Similar age-dependent patterns were not observed in the EL group, with GABA being consistently low across all timepoints. Integrated microbiome-metabolome analysis showed a positive correlation between GABA and Bifidobacterium species and negative associations with Clostridium species. In vitro experiments supported these observations demonstrating that bifidobacteria can produce GABA while clostridia can consume it. At the behavioral level, there were no significant differences between the EL and LL groups at 5 months. However, at 36 months of age, the EL group had significantly lower MSEL and ADOS-2 scores compared to the LL group. Taken together, the present results reveal early life alterations in gut microbiota composition and functionality in infants at elevated-likelihood of ASD. These changes occur before any behavioral impairments can be detected, supporting a possible role for the gut microbiota in emerging behavioral variability later in life.

Adolescent swimming exercise following maternal valproic acid treatment improves cognition and reduces stress-related symptoms in offspring mice: Role of sex and brain cytokines

Valproic acid (VPA) treatment during pregnancy is a risk factor for developing autism spectrum disorder, cognitive deficits, and stress-related disorders in children. No effective therapeutic strategies are currently approved to treat or manage core symptoms of autism. Active lifestyles and physical activity are closely associated with health and quality of life during childhood and adulthood. This study aimed to evaluate whether swimming exercise during adolescence can prevent the development of cognitive dysfunction and stress-related disorders in prenatally VPA-exposed mice offspring. Pregnant mice received VPA, afterwards, offspring were subjected to swimming exercise. We assessed neurobehavioral performances and inflammatory cytokines (interleukin-(IL)6, tumor-necrosis-factor-(TNF)α, interferon-(IFN)γ, and IL-17A) in the hippocampus and prefrontal cortex of offspring. Prenatal VPA treatment increased anxiety-and anhedonia-like behavior and decreased social behavior in male and female offspring. Prenatal VPA exposure also increased behavioral despair and reduced working and recognition memory in male offspring. Although prenatal VPA increased hippocampal IL-6 and IFN-γ, and prefrontal IFN-γ and IL-17 in males, it only increased hippocampal TNF-α and IFN-γ in female offspring. Adolescent exercise made VPA-treated male and female offspring resistant to anxiety-and anhedonia-like behavior in adulthood, whereas it only made VPA-exposed male offspring resistant to behavioral despair, social and cognitive deficits in adulthood. Exercise reduced hippocampal IL-6, TNF-α, IFN-γ, and IL-17, and prefrontal IFN-γ and IL-17 in VPA-treated male offspring, whereas it reduced hippocampal TNF-α and IFN-γ in VPA-treated female offspring. This study suggests that adolescent exercise may prevent the development of stress-related symptoms, cognitive deficits, and neuroinflammation in prenatally VPA-exposed offspring mice.

Investigating the Urinary Metabolome in the First Year of Life and Its Association with Later Diagnosis of Autism Spectrum Disorder or Non-Typical Neurodevelopment in the MARBLES Study.

Developmental disabilities are often associated with alterations in metabolism. However, it remains unknown how early these metabolic issues may arise. This study included a subset of children from the Markers of Autism Risks in Babies-Learning Early Signs (MARBLES) prospective cohort study. In this analysis, 109 urine samples collected at 3, 6, and/or 12 months of age from 70 children with a family history of ASD who went on to develop autism spectrum disorder (ASD n = 17), non-typical development (Non-TD n = 11), or typical development (TD n = 42) were investigated by nuclear magnetic resonance (NMR) spectroscopy to measure urinary metabolites. Multivariate principal component analysis and a generalized estimating equation were performed with the objective of exploring the associations between urinary metabolite levels in the first year of life and later adverse neurodevelopment. We found that children who were later diagnosed with ASD tended to have decreased urinary dimethylamine, guanidoacetate, hippurate, and serine, while children who were later diagnosed with Non-TD tended to have elevated urinary ethanolamine and hypoxanthine but lower methionine and homovanillate. Children later diagnosed with ASD or Non-TD both tended to have decreased urinary 3-aminoisobutyrate. Our results suggest subtle alterations in one-carbon metabolism, gut-microbial co-metabolism, and neurotransmitter precursors observed in the first year of life may be associated with later adverse neurodevelopment.

Perception of audio-visual synchrony in infants at elevated likelihood of developing autism spectrum disorder.

Findings suggest that early deficits in multisensory integration may impair language development among infants with elevated likelihood of developing ASD. •Perceptual integration of auditory and visual cues within speech is important for language development. •Prior work suggests that children with ASD are less sensitive to the temporal synchrony within audio-visual speech. •In this study, infants at elevated likelihood of developing ASD showed a larger temporal binding window for adynamic social event (Speaking Face) than TD infants, suggesting less efficient multisensory integration.

An approach for prevention planning based on the prevalence and comorbidity of neurodevelopmental disorders in 6-year-old children receiving primary care consultations on the island of Menorca

BackgroundFew studies have estimated the real prevalence of neurodevelopmental disorders according to the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) in Spain and worldwide. However, there are disparate prevalence figures. We consider research in this field essential to improve early detection, secondary prevention, and health planning.MethodsThe Minikid ADHD and TICS-Mini International Neuropsychiatric Interview for Children and Adolescents, the Autism Spectrum Quotient (Children’s version, AQ- Child) and a protocol of general medical questions were administered for screening purposes. The PROLEXIA battery for children aged from 4 to 6 years was used for direct assessments. Parents provided information on emotional, medical, and school aspects. The final population evaluated using these tools consisted of 291 6-year-old subjects.ResultsThe overall risk of presenting with a neurodevelopmental disorder was 55.4%. A 23.4% risk of presenting with attention-deficit/hyperactivity disorder (ADHD) in any modality (inattentive, hyperactive-impulsive and combined), a 2.8% risk of developing autism spectrum disorder (ASD), a 30.6% risk of presenting with a learning disorder with reading difficulties, a 5.5% risk of tics and a 22.5% risk of language problems (incomprehensible language or minor language problems) were detected in the sample. The most common combination of disorders was learning and language difficulties, accounting for 6.9% of the sample. The second most frequent combination was the presence of learning and language difficulties and ADHD, accounting for 4.5% of the sample.ConclusionsThe prevalence of risks detected in our sample seems to be consistent with national and international studies. A significant proportion of our sample had never been previously diagnosed (85%), so early detection programs are recommended.

Prader-Willy syndrome: heterogenous genetic mechanisms in a wide phenotypic spectrum

Prader-Willi syndrome (PWS) is an imprinted neuro-behavioral syndrome, affecting many organ systems, characterized by severe hypothalamic-pituitary dysfunction, severe hypotonia, feeding difficulties in the neonatal period, followed by hyperphagia with gradual development of morbid obesity since early childhood, short stature, hypogonadism, infertility, characteristic facial features, impaired motor and language development, cognitive impairment of varying degrees, delayed speech, increased risk of developing autism spectrum disorders (ASD), impaired social skills, and behavioral problems and / or severe psychiatric problems. Loss of expression of the preferentially paternally expressed of genes from the chromosomal region 15q11-q13 are the basis of pathogenesis of PWS, which occur through several mechanisms: deletion of 5-6 Mb DNA fragment from the 15q11-q13 region of the inherited paternal chromosome (65-75%), maternal uniparental disomy (mUPD) (in 20-30%) and Imprinting center (IC) defects, as microdeletions and epimutations (in 1-4%). In this paper, we present two cases diagnosed with PWS from our experience. The importance of diagnosis and familial recurrence risk will be discussed, as well as genotype-phenotype relationships in PWS. Patients with PWS should benefit from multidisciplinary management very early for greatly improving their quality of life, taking into consideration that obesity is a major factor influencing morbidity and mortality. In addition, a better understanding of the molecular basis of PWS pathogenesis offers hope for the development of new, revolutionary, epigenetic therapies in PWS, as well as in other genetic imprinting diseases.

Salivary oxytocin in autistic patients and in patients with intellectual disability.

Assessing the role of oxytocin (OT) in the regulation of social interaction is a promising area that opens up new opportunities for studying the mechanisms of developing autism spectrum disorders (ASD). To assess the correlation between the salivary OT level and age-related and psychopathological symptoms of children with intellectual disability (ID) and ASD. We used the clinical and psychopathological method to assess the signs of ASD based on International Classification of Diseases (ICD-10), the severity of ASD was specified by the selected Russian type version "Childhood Autism Rating Scale" (CARS). Patients of both groups had an IQ score below 70 points. The median and interquartile range of salivary OT levels in patients with ID and ASD were 23.897 [14.260-59.643] pg/mL, and in the group ID without ASD - Me = 50.896 [33.502-83.774] pg/mL (p = 0.001). The severity of ASD on the CARS scale Me = 51.5 [40.75-56.0] score in the group ID with ASD, and in the group ID without ASD-at the level of Me = 32 [27.0-38.0] points (p < 0.001). According to the results of correlation-regression analysis in the main group, a direct correlation was established between salivary OT level and a high degree of severity of ASD Rho = 0.435 (p = 0.005). There was no correlation between the salivary OT level and intellectual development in the group ID with ASD, Rho = 0.013 (p = 0.941) and we have found a relationship between oxytocin and intellectual development in the group ID without ASD, Rho = 0.297 (p = 0.005). There was no correlation between salivary OT and age, ASD and age. The results of this study indicate that patients in the group ID with ASD demonstrated a lower level of salivary OT concentration and a direct relationship between the maximum values of this indicator and the severity of autistic disorders, in contrast to patients in the group ID without ASD.

The Relationship Between Dietary Patterns and ASD

The dietary intake pattern of the mother when preparing for pregnancy, during pregnancy, and the nutritional exposure of the infant after birth have a bearing on the likelihood of the infant developing autism spectrum disorder (ASD). Many types of research have revealed a relationship between diet and the onset of ASD. However, it has not been established whether diet can be used to control the manifestation of ASD or in the prevention of ASD in unborn children. Therefore, there is an interest in ascertaining the main reasons for the relationship between dietary patterns and ASD. This paper analyzes studies about nutrition and its influence on ASD. In addition, the research explores the whole spectrum of environmental factors, namely external and internal ones, and their potential impact on an infant. Furthermore, the paper discusses the nutrition of the offspring and an approach to preventing the risk of ASD. The combination of different factors such as the mother's nutrition at various stages, the nutrition available to the infant, and the environment have been indicated in the results of the analysis to determine the level of risk for ASD in children. In this regard, further investigation of ASD prevention among infants is highly important and should be encouraged.

Study Protocol: Gut microbiota profiles implicated in the onset of autism spectrum disorders in preterm infants: A two-year follow-up study

IntroductionPreterm infants are at high-risk of developing autism spectrum disorders (ASD). The underlying mechanisms that explain the link between prematurity and ASD are unclear. Perinatal environmental factors may disrupt the gut-brain communication, when the gut microbiome composition is established and brain programming occurs. Therefore, the disruption of the gut-brain axis communication in response to perinatal environmental events may shed light on the association between prematurity and ASD.ObjectivesTo describe a new research project protocol which aim is to develop a dynamic model of gut microbiota variation in response to environmental factors that modulate the ASD risk in preterm infants.MethodsA two-year prospective observational study will be carried out, in which preterm infants will be assessed at birth, 40th postmenstrual week, at 6, 12, and 24 months of corrected age. Two-hundred preterm infants will be recruited. A comprehensive assessment will be conducted by collecting data on sociodemographic characteristics, medical history, family functioning, neurodevelopment, ASD screening, and diagnosis. Microbiome composition and microbial activity will be determined from feces.ResultsThe expected results are: i) to characterize ASD since its early manifestations in an at-risk population, allowing an early diagnosis and intervention to improve clinical outcomes; ii) to identify early microbiota biomarkers in order to find potential pathophysiological pathways; iii) to understand the protective and risk factors associated to ASD since perinatal period.ConclusionsA two-year predictive model will be generated based on environmental and gut microbiota variables. This predictive model of ASD would allow prevention, early diagnosis, improvement of prognosis, and personalized treatments in preterm infants.DisclosureNo significant relationships.